Treatment Patterns and Healthcare Resource Use in Medicare Beneficiaries with Parkinson’s Disease

Figures & data

Figure 1 Sample selection diagram.

Notes: ^aDiagnosis of PD was identified using International Classification of Diseases-9-Clinical Modification (ICD-9-CM) diagnosis code (332.0) or ICD-10-CM diagnosis code (G20). ^bDrug classes of interest included levodopa, dopamine agonists, monoamine oxidase type B inhibitors, and others (ie, amantadine, anticholinergics, catechol-O-methyltransferase inhibitors, and combination therapies).

Abbreviation: PD, Parkinson’s disease.

Table 1 Baseline Characteristics Stratified by Patient Cohort

Baseline Characteristics^a	Overall Cohort	Incident Cohort	Active Treatment Cohort
	N=318,582	N=214,829	N=234,298
Patient characteristics
Age at index date, years, mean ± SD^b	77.4 ± 7.0	77.6 ± 6.9	77.0 ± 6.8
Female, n (%)	169,942 (53.3)	109,722 (51.1)	122,663 (52.4)
Race, n (%)
Non-Hispanic White	266,584 (83.7)	179,910 (83.7)	198,003 (84.5)
Hispanic or Latino	20,418 (6.4)	13,799 (6.4)	14,205 (6.1)
Black	16,760 (5.3)	10,844 (5.0)	11,228 (4.8)
Asian or Pacific Islander	10,110 (3.2)	7084 (3.3)	7297 (3.1)
American Indian or Alaska Native	1095 (0.3)	696 (0.3)	822 (0.4)
Other or unknown	3615 (1.1)	2496 (1.2)	2743 (1.2)
Region, n (%)
Midwest	77,095 (24.2)	51,117 (23.8)	58,535 (25.0)
Northeast	63,670 (20.0)	46,304 (21.6)	44,374 (18.9)
South	122,325 (38.4)	79,558 (37.0)	90,517 (38.6)
West	54,860 (17.2)	37,437 (17.4)	40,441 (17.3)
Other or unknown^c	631 (0.2)	413 (0.2)	430 (0.2)
Year of index date, n (%)
2006–2009	102,372 (32.1)	67,043 (31.2)	74,057 (31.6)
2010–2013	101,644 (31.9)	68,906 (32.1)	74,800 (31.9)
2014–2017	114,566 (36.0)	78,880 (36.7)	85,441 (36.5)
Disease characteristics
CCI score, mean ± SD^d	1.5 ± 1.8	1.4 ± 1.7	1.4 ± 1.7
Comorbidities, n (%)
Hypertension	231,292 (72.6)	155,173 (72.2)	168,083 (71.7)
Diabetes	106,078 (33.7)	68,911‬ (33.5)	76,256‬ (33.0)
Coronary artery disease	88,970 (27.9)	59,719 (27.8)	63,628 (27.2)
Cerebrovascular disease	76,098 (24.2)	50,041 (23.6)	53,716 (23.2)
Chronic pulmonary disease	66,081 (21.0)	40,904 (19.3)	46,565 (20.1)
Peripheral vascular disease	64,641 (20.5)	41,930 (19.8)	44,825 (19.4)
Congestive heart failure	46,949 (14.9)	29,606 (14.0)	32,532 (14.1)
Anxiety	47,485 (14.9)	30,370 (14.1)	34,210 (14.6)
Dementia	46,506 (14.8)	29,688 (14.0)	29,653 (12.8)
Any malignancy	34,638 (11.0)	24,377 (11.5)	25,569 (11.0)
PD symptoms, n (%)
Motor symptoms	131,453 (41.3)	84,427 (39.3)	98,391 (42.0)
Gait impairment	82,622 (25.9)	52,591 (24.5)	61,586 (26.3)
Tremor	38,739 (12.2)	24,434 (11.4)	30,570 (13.0)
Dysphagia	23,751 (7.5)	14,871 (6.9)	16,556 (7.1)
Speech disturbance	17,943 (5.6)	11,960 (5.6)	13,046 (5.6)
Dystonia	3474 (1.1)	1449 (0.7)	2481 (1.1)
Severe motor symptoms	59,160 (18.6)	38,236 (17.8)	42,234 (18.0)
Use of wheelchair or other enabling machines and devices	36,654 (11.5)	23,394 (10.9)	26,435 (11.3)
Falls	30,030 (9.4)	19,626 (9.1)	21,184 (9.0)
Sleep disorders (ie, sleep disturbance)	39,047 (12.3)	23,553 (11.0)	29,088 (12.4)
Neuropsychiatric symptoms	120,394 (37.8)	76,650 (35.7)	82,832 (35.4)
Depression	75,179 (23.6)	47,253 (22.0)	53,615 (22.9)
Cognitive/memory impairment (eg, dementia, mild cognitive impairment)	74,907 (23.5)	47,926 (22.3)	48,839 (20.8)
Hallucination	3083 (1.0)	1824 (0.8)	2067 (0.9)
Impulse control disorder	686 (0.2)	357 (0.2)	460 (0.2)
Other non-motor symptoms	39,122 (12.3)	26,587 (12.4)	29,167 (12.4)
Frequency of micturition, urgency of urination or nocturia	31,588 (9.9)	21,393 (10.0)	23,799 (10.2)
Orthostatic hypotension	8257 (2.6)	5679 (2.6)	5887 (2.5)
Smell and taste disturbance	646 (0.2)	455 (0.2)	488 (0.2)

Notes: ^aThe baseline period was defined as the 6 months prior to the index date. ^bThe index date was defined as the date of the first PD diagnosis in the data. ^cOther or unknown region included Puerto Rico, Virgin Islands, Canada and Islands, Central America and West Indies, Europe, Philippines, American Samoa, Northern Marianas, Guam or otherwise unknown regions. ^dCCI was calculated based on methods outlined in Quan, Hude, et al. Coding algorithms for defining comorbidities in ICD-9-CM and ICD-10 administrative data. Medical care (2005): 1130–1139.

Abbreviations: CCI, Charlson Comorbidity Index; ICD-9/10-CM, International Classification of Diseases-9/10-Clinical Modification; PD, Parkinson’s disease; SD, standard deviation.

Figure 2 Treatment patterns of incident cohort. (A) Distribution of first, second, and third lines of therapy; (B) levodopa dosing; (C) time to treatment initiation; (D) time to treatment discontinuation.

Notes: ^a“Other therapies” included amantadine, anticholinergics, catechol-O-methyltransferase inhibitor, levodopa inhaler, istradefylline, and Stalevo. ^b“Other regimens with N<1000” included regimens with a sample size of less than 1000 within each line of therapy. ^c“No further treatment” included patients who did not have treatment claims in the current line among those who have received treatment in the previous line. The counts included those who were censored at this line. ^dThe outcome event was defined as initiation of first PD treatment. Patients were censored at the end of study follow-up period. ^eThe outcome event was defined as 1L discontinuation. Patients were censored at the end of study follow-up period.

Abbreviations: 1L, first line; 2L, second line; 3L, third line; CI, confidence interval; DAs, dopamine agonists; MAO-B, monoamine oxidase B; NR, not reached; PD, Parkinson’s disease; SD, standard deviation.

Table 2 All-Cause HRU Over 6-Month Cycles Associated with PD Symptoms Among Overall Cohort

PD Symptom	Rate of HRU per 6-Month Cycle, Mean ± SD [Median]		Multivariable Model^a,b
	With Symptoms	Without Symptoms	IRR	95% CI	p-value
Motor symptoms^c
Inpatient visits	0.7 ± 1.4 [0.0]	0.2 ± 0.9 [0.0]	2.14	(2.12, 2.16)	<0.0001*
Outpatient physician or specialty visits	10.9 ± 7.9 [9.0]	8.2 ± 6.7 [7.0]	1.26	(1.26, 1.26)	<0.0001*
SNF/LTC visits	7.3 ± 8.4 [4.0]	3.9 ± 6.0 [1.0]	1.57	(1.56, 1.57)	<0.0001*
ER visits	0.5 ± 1.0 [0.0]	0.3 ± 0.7 [0.0]	1.41	(1.40, 1.42)	<0.0001*
Severe motor symptoms^d
Inpatient visits	0.9 ± 1.6 [0.0]	0.3 ± 1.0 [0.0]	2.30	(2.29, 2.32)	<0.0001*
Outpatient physician or specialty visits	11.4 ± 7.9 [10.0]	8.9 ± 7.1 [7.0]	1.19	(1.19, 1.19)	<0.0001*
SNF/LTC visits	7.6 ± 8.0 [5.0]	4.9 ± 7.1 [2.0]	1.33	(1.33, 1.34)	<0.0001*
ER visits	0.8 ± 1.2 [0.0]	0.3 ± 0.7 [0.0]	2.58	(2.57, 2.60)	<0.0001*
Sleep disorders^e
Inpatient visits	0.6 ± 1.3 [0.0]	0.4 ± 1.1 [0.0]	1.39	(1.38, 1.41)	<0.0001*
Outpatient physician or specialty visits	12.0 ± 7.8 [11.0]	8.8 ± 7.1 [7.0]	1.24	(1.24, 1.25)	<0.0001*
SNF/LTC visits	6.2 ± 7.4 [4.0]	5.2 ± 7.3 [2.0]	1.21	(1.20, 1.22)	<0.0001*
ER visits	0.5 ± 1.1 [0.0]	0.3 ± 0.8 [0.0]	1.30	(1.29, 1.31)	<0.0001*
Neuropsychiatric symptoms^f
Inpatient visits	0.6 ± 1.4 [0.0]	0.2 ± 0.8 [0.0]	2.13	(2.11, 2.15)	<0.0001*
Outpatient physician or specialty visits	9.2 ± 7.5 [8.0]	9.5 ± 7.2 [8.0]	0.89	(0.89, 0.90)	<0.0001*
SNF/LTC visits	7.9 ± 8.5 [6.0]	3.0 ± 4.9 [1.0]	2.14	(2.13, 2.15)	<0.0001*
ER visits	0.5 ± 1.0 [0.0]	0.2 ± 0.6 [0.0]	1.60	(1.58, 1.61)	<0.0001*
Other non-motor symptoms^g
Inpatient visits	0.6 ± 1.3 [0.0]	0.4 ± 1.1 [0.0]	1.32	(1.31, 1.33)	<0.0001*
Outpatient physician or specialty visits	12.7 ± 7.9 [11.0]	8.8 ± 7.1 [7.0]	1.34	(1.33, 1.34)	<0.0001*
SNF/LTC visits	5.1 ± 6.8 [2.0]	5.4 ± 7.4 [2.0]	0.92	(0.91, 0.92)	<0.0001*
ER visits	0.6 ± 1.1 [0.0]	0.3 ± 0.8 [0.0]	1.40	(1.39, 1.41)	<0.0001*

Notes: *Indicates significant at the 5% level. ^aIRRs and 95% CIs were estimated using negative binomial mixed effects models. ^bThe multivariable models were adjusted for baseline characteristics, including age, sex, race, state, calendar year of the first PD diagnosis, CCI score and the other PD symptoms. ^cMotor symptoms included dystonia, speech disturbance, dysphagia, gait impairment, and tremor. ^dSevere motor symptoms included falls and use of wheelchair or other enabling machines and devices. ^eSleep disorders referred to sleep disturbance. ^fNeuropsychiatric symptoms included hallucination, impulse control disorder, cognitive/memory impairment (eg, dementia, mild cognitive impairment), and depression. ^gOther non-motor symptoms included orthostatic hypotension, urinary symptoms (frequency of micturition, urgency of urination, or nocturia), and smell and taste disturbance.

Abbreviations: CCI, Charlson Comorbidity Index; CI, confidence interval; IRR, incidence rate ratio; ER, emergency room; HRU, healthcare resource utilization; PD, Parkinson’s disease; SD, standard deviation; SNF/LTC, skilled nursing facility or long-term care visits.

Table 3 All-Cause HRU Over 6-Month Cycles Associated with Drug-Specific AEs Among Active Treatment Cohort

Drug-Specific AEs	Rate of HRU per 6-Month Cycle, Mean ± SD [Median]		Multivariable Model^a,b
	With AEs	Without AEs	IRR	95% CI	p-value
Dyskinesia
Inpatient visits	0.7 ± 1.5 [0.0]	0.4 ± 1.1 [0.0]	1.68	(1.66, 1.70)	<0.0001*
Outpatient physician or specialty visits	11.6 ± 7.5 [10.0]	9.4 ± 7.3 [8.0]	1.24	(1.24, 1.25)	<0.0001*
SNF/LTC visits	5.1 ± 7.1 [2.0]	5.2 ± 7.2 [2.0]	0.97	(0.96, 0.98)	<0.0001*
ER visits	0.5 ± 1.1 [0.0]	0.4 ± 0.8 [0.0]	1.44	(1.42, 1.46)	<0.0001*
Somnolence
Inpatient visits	0.7 ± 1.4 [0.0]	0.4 ± 1.1 [0.0]	1.71	(1.68, 1.75)	<0.0001*
Outpatient physician or specialty visits	13.2 ± 8.0 [12.0]	9.4 ± 7.3 [8.0]	1.34	(1.33, 1.36)	<0.0001*
SNF/LTC visits	6.6 ± 7.1 [4.0]	5.2 ± 7.2 [2.0]	1.35	(1.33, 1.37)	<0.0001*
ER visits	0.6 ± 1.1 [0.0]	0.4 ± 0.8 [0.0]	1.60	(1.57, 1.64)	<0.0001*
Hallucination
Inpatient visits	1.0 ± 1.7 [0.0]	0.4 ± 1.1 [0.0]	2.40	(2.36, 2.44)	<0.0001*
Outpatient physician or specialty visits	10.3 ± 7.1 [9.0]	9.5 ± 7.3 [8.0]	1.06	(1.05, 1.06)	<0.0001*
SNF/LTC visits	7.7 ± 8.5 [5.0]	5.2 ± 7.2 [2.0]	1.61	(1.59, 1.64)	<0.0001*
ER visits	0.8 ± 1.2 [0.0]	0.4 ± 0.8 [0.0]	2.10	(2.07, 2.14)	<0.0001*
Impulse control disorder
Inpatient visits	1.4 ± 2.6 [0.0]	0.4 ± 1.1 [0.0]	3.00	(2.84, 3.18)	<0.0001*
Outpatient physician or specialty visits	8.7 ± 7.4 [7.0]	9.5 ± 7.3 [8.0]	0.87	(0.84, 0.90)	<0.0001*
SNF/LTC visits	11.4 ± 9.5 [10.0]	5.2 ± 7.2 [2.0]	2.12	(2.04, 2.21)	<0.0001*
ER visits	0.9 ± 1.4 [0.0]	0.4 ± 0.8 [0.0]	2.24	(2.12, 2.36)	<0.0001*

Notes: *Indicates significant at the 5% level. ^aIRRs and 95% CIs were estimated using negative binomial mixed effects models. ^bThe multivariable models were adjusted for baseline characteristics, including age, sex, race, state, calendar year of the first PD diagnosis, CCI score and the other PD symptoms.

Abbreviations: AEs, adverse events; CCI, Charlson Comorbidity Index; CI, confidence interval; IRR, incidence rate ratio; ER, emergency room; HRU, healthcare resource utilization; PD, Parkinson’s disease; SD, standard deviation; SNF/LTC, skilled nursing facility or long-term care.

Table 4 All-Cause Healthcare Costs Over 6-Month Cycles Associated with PD Symptoms Among Overall Cohort

PD Symptom	Costs Per 6-Month Cycle, Mean ± SD [Median]		Multivariable Model^a,b
	With Symptoms	Without Symptoms	Cost Difference	95% CI	p-value
Motor symptoms^c
Medical costs	16,839 ± 24,656 [6641]	6183 ± 12,156 [1788]	7369	(7317, 7420)	<0.0001*
Inpatient costs	3053 ± 11,031 [0]	825 ± 4994 [0]	1563	(1543, 1584)	<0.0001*
Pharmacy costs	1708 ± 4696 [789]	1416 ± 3873 [669]	125	(109, 140)	<0.0001*
Severe motor symptoms^d
Medical costs	22,416 ± 27,723 [11,469]	8295 ± 15,960 [2473]	10,712	(10,637, 10,788)	<0.0001*
Inpatient costs	4431 ± 12,836 [0]	1220 ± 6738 [0]	2545	(2512, 2579)	<0.0001*
Pharmacy costs	1822 ± 4979 [817]	1483 ± 4076 [699]	156	(138, 174)	<0.0001*
Sleep disorders^e
Medical costs	15,641 ± 23,788 [5806]	9841 ± 18,212 [2811]	3203	(3128, 3278)	<0.0001*
Inpatient costs	3081 ± 10,889 [0]	1531 ± 7588 [0]	936	(905, 967)	<0.0001*
Pharmacy costs	1940 ± 5557 [793]	1461 ± 3923 [706]	315	(290, 341)	<0.0001*
Neuropsychiatric symptoms^f
Medical costs	15,649 ± 23,440 [6015]	6284 ± 13,065 [1950]	5809	(5757, 5862)	<0.0001*
Inpatient costs	2648 ± 10,072 [0]	995 ± 5990 [0]	968	(949, 988)	<0.0001*
Pharmacy costs	1810 ± 4378 [886]	1291 ± 4119 [579]	350	(333, 368)	<0.0001*
Other non-motor symptoms^g
Medical costs	14,699 ± 22,294 [5638]	10,263 ± 18,878 [2922]	2219	(2147, 2291)	<0.0001*
Inpatient costs	2843 ± 10,261 [0]	1642 ± 7921 [0]	663	(631, 695)	<0.0001*
Pharmacy costs	1909 ± 5621 [840]	1489 ± 4005 [702]	378	(350, 407)	<0.0001*

Notes: *Indicates significant at the 5% level. ^aCost differences and 95% CIs were estimated using linear mixed effects models. Costs were inflated to 2020 United States dollars. ^bThe multivariable models were adjusted for baseline characteristics, including age, sex, race, state, calendar year of the first PD diagnosis, CCI score and the other PD symptoms. ^cMotor symptoms included dystonia, speech disturbance, dysphagia, gait impairment, and tremor. ^dSevere motor symptoms included falls and use of wheelchair or other enabling machines and devices. ^eSleep disorders referred to sleep disturbance. ^fNeuropsychiatric symptoms included hallucination, impulse control disorder, cognitive/memory impairment (eg, dementia, mild cognitive impairment), and depression. ^gOther non-motor symptoms included orthostatic hypotension, urinary symptoms (frequency of micturition, urgency of urination, or nocturia), and smell and taste disturbance.

Abbreviations: CCI, Charlson Comorbidity Index; CI, confidence interval; PD, Parkinson’s disease; SD, standard deviation.

Table 5 All-Cause Healthcare Costs Over 6-Month Cycles Associated with Drug-Specific AEs Among Active Treatment Cohort

Drug-Specific AE	Costs Per 6-Month Cycle, Mean ± SD [Median]		Multivariable Model^a,b
	With AEs	Without AEs	Cost Difference	95% CI	p-value
Dyskinesia
Medical costs	14,939 ± 23,320 [5072]	10,500 ± 18,859 [3115]	4171	(4044, 4298)	<0.0001*
Inpatient costs	3230 ± 10,977 [0]	1703 ± 7966 [0]	1468	(1409, 1528)	<0.0001*
Pharmacy costs	1890 ± 5535 [890]	1589 ± 4209 [754]	24	(−6, 53)	0.114
Somnolence
Medical costs	17,829 ± 26,665 [6814]	10,645 ± 19,007 [3163]	6097	(5828, 6365)	<0.0001*
Inpatient costs	3490 ± 12,552 [0]	1766 ± 8087 [0]	1470	(1347, 1594)	<0.0001*
Pharmacy costs	2058 ± 5346 [967]	1599 ± 4280 [760]	82	(31, 134)	0.002
Hallucination
Medical costs	21,111 ± 26,929 [9927]	10,517 ± 18,891 [3137]	10,875	(10,638, 11,111)	<0.0001*
Inpatient costs	4184 ± 12,096 [0]	1738 ± 8061 [0]	2469	(2365, 2574)	<0.0001*
Pharmacy costs	2326 ± 6032 [882]	1590 ± 4249 [761]	530	(474, 586)	<0.0001*
Impulse control disorder
Medical costs	23,740 ± 29,864 [10,653]	10,733 ± 19,138 [3204]	11,717	(10,848, 12,586)	<0.0001*
Inpatient costs	5643 ± 13,985 [0]	1785 ± 8164 [0]	3601	(3212, 3991)	<0.0001*
Pharmacy costs	2290 ± 3729 [1215]	1605 ± 4303 [762]	39	(−80, 159)	0.521

Notes: *Indicates significant at the 5% level. ^aCost differences and 95% CIs were estimated using linear mixed effects models. Costs were inflated to 2020 United States dollars. ^bThe multivariable models were adjusted for baseline characteristics, including age, sex, race, state, calendar year of the first PD diagnosis, CCI score, and the other drug-specific AEs.

Abbreviations: AEs, adverse events; CCI, Charlson Comorbidity Index; CI, confidence interval; PD, Parkinson’s disease; SD, standard deviation.